Continued support is requested to further develop flow cytometry (FCM) as a diagnostic and prognostic tool for the management of patients with malignant lymphomas employing genotypic, phenotypic, cytokinetic and therapy-related parameters. These studies will focus on the two major subgroups of diffuse large cell (DLCL) and follicular small cleaved lymphoma (FSCL) to systematically examine the heterogeneity in lineage, differentiation, proliferation, pertinent oncogene products including receptors, and therapy- related cellular features (e.g. expression of glucocorticoid and interferon receptors, multidrug resistance phenotype and adriamycin cellular uptake). Multiparameter FCM technology will be employed to study the interaction between these cellular features and their expression in relationship to tumor cells defined either on the basis of DNA aneuploidy or monoclonal light chain reactivity. Advances are anticipated in the understanding of the fundamentally different clinical behavior of follicular small cleaved vs diffuse large cell lymphomas and the biologically intriguing issue of transformation from low to higher histologic grade. A second segment of this proposal is directed to develop new cytometric probes to study the molecular mechanisms of neoplasia including oncogene products related to growth and differentiation and expression of cellular receptors. As result of this research, we anticipate major progress towards biologically and molecularly based objective and quantitative diagnosis of lymphomas, where morphologic interpretation has been fraught with problems of reproducibility and clinical relevance.